The present invention, in some embodiments thereof, relates to Brucella phage nucleic acid sequences and uses thereof.
Brucella are Gram negative, small coccobacilli bacteria. They are animal pathogens causing abortions in the natural hosts, in the latest period of pregnancy. Genus Brucella includes 10 species divided to smooth and rough outer membrane LPS bearing organisms. Three smooth Brucella species, (B. melitensis, B. abortus and B. suis) associated with small ruminant, bovid and swine brucellosis, respectively, are zoonotic to humans. Less frequently, B. ceti and B. pinnipedialis associated with marine mammal brucellosis have been documented as causative agents of human brucellosis. In addition, B. canis that is associated with canine brucellosis is a rough organism that causes human infection. The disease in humans is presented as undulant fever also known as Malta fever, and it may sequel to a chronic disease or manifestation of meningitis, osteomyelitis, endocarditis and other complications. In rare occasions the disease may become fatal.
Brucella phages are bacterial viruses specific to Brucella species. A review of Brucella phages and their taxonomical relatedness was published in 1981. All contemporarily known Brucella phages were shown to comprise a similar icosahedral head and short tail morphology belonging to the family Podoviradae. The studied phages were shown to be closely related according to antigenic and physiological properties and resistance to chemical and physical agents. These findings have led the authors to include the summarized variants within a single species and propose phage Tb as type virus (Ackerman, H.-W., Simon, F., and Verger, J.-M. 1981. Intervirology 16: 1-7).
Brucella phages have linear double stranded DNA in size around 38 kilo base pairs. Restriction enzyme digestion analyses of phages Tb, Fi, Wb, Iz and R/C have shown similarity amongst the DNAs and little evidence has been found for lysogenic existence of the phages or presence of plasmid forms in the hosts.
Previous studies have established guanosine—cytosine content of 45.3-46.7% in phage Tb whereas a higher percentage of 48.9% was anticipated in other phages.
Use of phages as therapeutic agents of a pathogenic disease has been indicated by several researchers (Brussow, H. 2005. Microbiol. 151: 2133-2140; Summers, W. C. 2001. Ann. Rev. Microbiol. 55: 437-451).
In addition, Brucella phages have been employed in Brucella typing and a phage susceptibility test has become instrumental in classification and establishing a taxonomical tree of genus Brucella. Specifically, it was suggested that division of genus Brucella into nomen-species is partly justified according to their species specific phage susceptibilities that also correlated well with host affiliation of the strains. Brucella phages have been divided into 7 groups according to their infectivity to Brucella spp. Phage Izatnagar (Iz1) represents group 6 that is infective to all smooth Brucella nomenspecies and partly to rough strains (Corbel and Tolari, 1988, Res Vet Sci; 44: 45-49).
Zhu et al., 2009 [ Int. J. Mol. Sci. 10: 2999-3011] teaches a partial sequence for the Tb (Tbilisi) Brucella phage.
Rigby et al., 1989 [ Can J Vet Res. 53: 319-325] teaches a partial sequence for Nepean phage and other lytic phages of Brucella species.
U.S. Patent No. 20030017449 teaches detection of Brucella using Brucella phage.